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Werner Syndrome Protein and DNA Replication
Werner Syndrome (WS) is an autosomal recessive disorder characterized by the premature development of aging features. Individuals with WS also have a greater predisposition to rare cancers that are mesenchymal in origin. Werner Syndrome Protein (WRN), the protein mutated in WS, is unique among RecQ...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274846/ https://www.ncbi.nlm.nih.gov/pubmed/30400178 http://dx.doi.org/10.3390/ijms19113442 |
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author | Mukherjee, Shibani Sinha, Debapriya Bhattacharya, Souparno Srinivasan, Kalayarasan Abdisalaam, Salim Asaithamby, Aroumougame |
author_facet | Mukherjee, Shibani Sinha, Debapriya Bhattacharya, Souparno Srinivasan, Kalayarasan Abdisalaam, Salim Asaithamby, Aroumougame |
author_sort | Mukherjee, Shibani |
collection | PubMed |
description | Werner Syndrome (WS) is an autosomal recessive disorder characterized by the premature development of aging features. Individuals with WS also have a greater predisposition to rare cancers that are mesenchymal in origin. Werner Syndrome Protein (WRN), the protein mutated in WS, is unique among RecQ family proteins in that it possesses exonuclease and 3′ to 5′ helicase activities. WRN forms dynamic sub-complexes with different factors involved in DNA replication, recombination and repair. WRN binding partners either facilitate its DNA metabolic activities or utilize it to execute their specific functions. Furthermore, WRN is phosphorylated by multiple kinases, including Ataxia telangiectasia mutated, Ataxia telangiectasia and Rad3 related, c-Abl, Cyclin-dependent kinase 1 and DNA-dependent protein kinase catalytic subunit, in response to genotoxic stress. These post-translational modifications are critical for WRN to function properly in DNA repair, replication and recombination. Accumulating evidence suggests that WRN plays a crucial role in one or more genome stability maintenance pathways, through which it suppresses cancer and premature aging. Among its many functions, WRN helps in replication fork progression, facilitates the repair of stalled replication forks and DNA double-strand breaks associated with replication forks, and blocks nuclease-mediated excessive processing of replication forks. In this review, we specifically focus on human WRN’s contribution to replication fork processing for maintaining genome stability and suppressing premature aging. Understanding WRN’s molecular role in timely and faithful DNA replication will further advance our understanding of the pathophysiology of WS. |
format | Online Article Text |
id | pubmed-6274846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62748462018-12-15 Werner Syndrome Protein and DNA Replication Mukherjee, Shibani Sinha, Debapriya Bhattacharya, Souparno Srinivasan, Kalayarasan Abdisalaam, Salim Asaithamby, Aroumougame Int J Mol Sci Review Werner Syndrome (WS) is an autosomal recessive disorder characterized by the premature development of aging features. Individuals with WS also have a greater predisposition to rare cancers that are mesenchymal in origin. Werner Syndrome Protein (WRN), the protein mutated in WS, is unique among RecQ family proteins in that it possesses exonuclease and 3′ to 5′ helicase activities. WRN forms dynamic sub-complexes with different factors involved in DNA replication, recombination and repair. WRN binding partners either facilitate its DNA metabolic activities or utilize it to execute their specific functions. Furthermore, WRN is phosphorylated by multiple kinases, including Ataxia telangiectasia mutated, Ataxia telangiectasia and Rad3 related, c-Abl, Cyclin-dependent kinase 1 and DNA-dependent protein kinase catalytic subunit, in response to genotoxic stress. These post-translational modifications are critical for WRN to function properly in DNA repair, replication and recombination. Accumulating evidence suggests that WRN plays a crucial role in one or more genome stability maintenance pathways, through which it suppresses cancer and premature aging. Among its many functions, WRN helps in replication fork progression, facilitates the repair of stalled replication forks and DNA double-strand breaks associated with replication forks, and blocks nuclease-mediated excessive processing of replication forks. In this review, we specifically focus on human WRN’s contribution to replication fork processing for maintaining genome stability and suppressing premature aging. Understanding WRN’s molecular role in timely and faithful DNA replication will further advance our understanding of the pathophysiology of WS. MDPI 2018-11-02 /pmc/articles/PMC6274846/ /pubmed/30400178 http://dx.doi.org/10.3390/ijms19113442 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Mukherjee, Shibani Sinha, Debapriya Bhattacharya, Souparno Srinivasan, Kalayarasan Abdisalaam, Salim Asaithamby, Aroumougame Werner Syndrome Protein and DNA Replication |
title | Werner Syndrome Protein and DNA Replication |
title_full | Werner Syndrome Protein and DNA Replication |
title_fullStr | Werner Syndrome Protein and DNA Replication |
title_full_unstemmed | Werner Syndrome Protein and DNA Replication |
title_short | Werner Syndrome Protein and DNA Replication |
title_sort | werner syndrome protein and dna replication |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274846/ https://www.ncbi.nlm.nih.gov/pubmed/30400178 http://dx.doi.org/10.3390/ijms19113442 |
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